Background. Obesity is often associated with the development of heart failure but the precise mechanisms remain uncertain. The purpose of this study was to evaluate the key components of Fas receptor-dependent apoptotic pathway in excised hearts from obese Zucker rats. Methods. Twelve obese Zucker rats were studied at 5~6 months of age and twelve age-matched lean Zucker rats served as control. The myocardial architecture, key components of Fas receptor-dependent apoptotic pathway, apoptotic activity, and fibrosis in the excised left ventricle from rats were measured by Hematoxylin-eosin staining, Western blotting, RT-PCR, TUNEL assay and Masson trichrome staining. Results. The ratios of whole heart weight to tibia length were significantly increased in the obese group. Cardiomyocyte disarray, increased interstitial space, TUNEL-positive cardiac myocytes and minor cardiac fibrosis were observed in obese rat hearts. The Fas ligand, Fas death receptors, and FADD were all significantly increased in obese rat hearts. In addition, pro-caspase-8 and pro-caspase-3 were significantly decreased whereas activated caspase-8 and activated caspase-3 were significantly increased in obese rat hearts, compared with lean rat heart, imply pro-forms of caspase-8 and caspase-3 were cleaved into active-forms caspase-8 and caspase-3. Conclusions. The cardiac Fas receptor-dependent apoptotic pathways were more activated in obese rat hearts, which may provide one of possible apoptotic mechanism for developing heart failure in obesity.
